33 Lipomelanin sunscreen composition

ABSTRACT

A novel lipomelanin sunscreen complex includes melanin linked to a lipid to form a lipomelanin. One or more ultra-violet-light absorbing compounds can be added to form a lipomelanin sunscreen complex. A method for making the complex includes the oxidization of DOPA in the presence of a lipid and one or more ultra-violet absorbing compounds to form a mixture and precipitating the complex from the mixture by the addition of acid. The lipomelanin sunscreen complex provides protection against harmful ultra-violet radiation. The level of UV protection may be varied according to the presence and properties of the ultra-violet absorbing compounds in the complex.

This application is a division of U.S. patent application Ser. No.08/054,271 filed on Apr. 30, 1993 which issued on Jul. 1, 1997 as U.S.Pat. No. 5,643,554.

FIELD OF THE INVENTION

The present invention relates to novel sunscreen complexes.

In particular, the present invention relates to ultra-violet-lightabsorbing compositions containing melanin.

BACKGROUND OF THE INVENTION

Melanins are the major pigments of hair, skin and eyes. Naturallyoccurring melanins can be of a variety of colours, such as black, brownand red. Two major categories of melanins are known; eumelanins whichprovide a black or brown pigmentation, and pheomelanins, which provide ayellow to reddish-brown pigmentation. Natural suntanning occurs throughexposure of the skin to light radiation at a wavelength of 280-400 nm.

For most individuals the sensitivity of the skin to ultra-violetradiation (hereinafter referred to as "UVR") is largely determined byits melanin content. The amounts and types of melanin present in theskin vary from person to person and, thus, the tolerance of the skinwhen exposed to UVR varies from person to person. For most individualsthe greater the melanin content of the skin of an individual, the moretolerant is the skin of that individual to UVR.

Melanins are complex heteropolymers, of which the biosynthetic pathwaysand exact chemical structure are unknown. However, melanins are believedto be copolymers of 3,4-dihydroxyphenylalanine (DOPA) and cysteinyldopa.While the inventors do not intend to be limited to any particular schemeof synthesis, it is believed that the in vivo synthetic pathway leadingto the production of melanin begins with the enzymatic oxidation of theamino acid, tyrosine, to form DOPA, and continues in the presence of theenzyme tyrosinase (polyphenol oxidase) with a series of oxidation andpolymerization reactions to result in melanin. This postulated syntheticpathway may be represented as follows: ##STR1##

Melanins may also be produced by the auto-oxidation of DOPA, whereby theproduction of melanin occurs in the absence of tyrosinase.

Thus, it is believed that known melanins, or compounds with the same orsimilar functional features as known melanins, may be produced eithernaturally or synthetically from DOPA, analogs of DOPA or biosyntheticprecursors of DOPA. As used herein, "melanins" includes all such knownmelanins or melanin products, however derived, and all melanin-likecompounds or analogs with the herein-described pigment andphotoprotective functions.

The photoprotective function of melanin is believed to be associatedwith both its physical and biochemical properties. Melanin is believedto dissipate UVR into heat which is absorbed, and to promote oxidationreactions and quench free radicals, the formation of which is induced byUVR. Melanin is able to function as a stable free radical, thusresulting in its ability to quench damaging free radicals formed in theskin on exposure to UVR. The role of melanin as a free radical scavengeris significant in its photoprotective role in individuals having amoderate or greater melanin content in their skin; however, it is highlydesirable that individuals having a minimal melanin content in theirskin supplement the body's natural protective mechanism to UVR with atopical sunscreen supplement. It is now recognized that even individualswith moderate or greater levels of melanin should supplement thisnatural protective mechanism when longer exposure to UVR is anticipated.

As a result of the increasing awareness of the public of the detrimentaleffects of exposure to UVR, a variety of sunscreen compositions fortopical administration have been developed. Various salicylate compoundshave been described as sunscreen agents due to their ability to absorbUVR. For example, U.S. Pat. Nos. 3,506,758 and 4,256,664 describecompositions for use as sunscreens which include the esterificationproduct of p-aminobenzoic acid (paba) and/or salicylic acid withlecithins, choline and/or imidazoles having a reactive hydroxyl group.U.S. Pat. No. 4,454,112 describes tocopherol acetylsalicylate compoundswhich are useful as sunscreen agents in compositions for topicaladministration. However, it has been found that salicylate compounds maycause skin irritations and allergic reactions in some individuals, and,as a result, are not ideal as the primary components of such topicalcompositions.

A common UVR absorbing compound found in sunscreen compositions is paba,and esters of paba, such as octyl dimethyl pabaoctyl-p-(dimethyl-amino)benzoate!. U.S. Pat. No. 4,434,154 teaches onesuch UVR protective composition which contains an emulsion of octyldimethyl paba, dihydroxy acetone, water, oil and a surfactant.

Sun protectant compositions have also been described which containmelanin. However, the known methods of making melanin havedisadvantages. With both the enzymatic and auto-oxidation methods forpreparing melanins, the properties of the melanin product obtained makeit undesirable for incorporation into a sunscreen composition forapplication onto the skin. Specifically, the melanins obtained aregranular in nature, which results in a product that cannot be spreadevenly when applied to the skin. These melanins are also undesirable inthat they are not easily absorbed by the skin under acceptablephysiological skin conditions (i.e. neutral pH). Further, theeffectiveness of these melanins is limited with respect to ultra-violetabsorption. Specifically, the absorption capacity of the melaninsproduced by either of these methods is low in the short-wave range (UVB)of the ultra-violet spectrum. U.S. Pat. No. 4,806,344 describes one suchmelanin composition additionally comprising ferric chloride,triethanolamine, a sunscreen compound such as paba and a cosmetic basein the form of an oil, cream or ointment.

Many of the sunscreen products currently available do not fully protectthe skin against the complete wavelength spectrum of UVR. UVR comprisesboth long-wave UVR (or UVA, having a wavelength of approximately 320-400nm) and short-wave UVR (or UVB, having a wavelength of approximately290-320 nm). Of particular concern for a large portion of the populationis protection of the skin against the aging process which is acceleratedby exposure to UVR. Long-wave UVA is believed to specifically contributeto the aging process.

Most ultra-violet light absorbing compounds useful as sunscreen agentsonly absorb within a small range of the wavelength of UVR. Thus, inorder to maximize the absorption capacity of UVR in a sunscreencomposition, the composition may contain not just a single sunscreencompound but several such compounds which are selected to provide broadrange UVR protection. However, sunscreen compositions containing avariety of compounds are more apt to cause allergic or photoallergicreactions in individuals. Allergic and photoallergic reactions toexisting sunscreen compounds and compositions is a common occurrence andgenerally results in dermatitis or photodermatitis. Certain individualsalso suffer from skin eruptions due to long UVA and visible light, and avery broad wavelength sunscreen would be valuable for these people.

Thus, it would be desirable to provide a sunscreen composition whichimparts effective protection against the broad spectrum of UVR, which iscompatible for use with human skin tissue.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novelmelanin-containing compounds, and a method for making such compounds.

Accordingly, in one aspect, the present invention provides a lipomelanincomposition formed from a melanin chemically bonded to a lipid. Inanother aspect of the present invention, there is provided a lipomelaninsunscreen complex comprising a melanin bonded to a lipid to form alipomelanin, wherein said lipomelanin incorporates at least oneultra-violet light absorbing compound.

In yet another aspect of the present invention, there is provided amethod for making a lipomelanin comprising the steps of enzymaticallyconverting 3,4-dihydroxyphenylalanine or a suitable analog thereof tomelanin, in the presence of a lipid, and isolating the resultinglipomelanin.

In a further aspect of the present invention, there is provided a methodfor making a lipomelanin sunscreen comprising a melanin chemicallybonded to a lipid compound to form a lipomelanin wherein saidlipomelanin also includes at least one ultra-violet-light absorbingcompound, including the steps of enzymatically converting3,4-dihydroxyphenylalanine or a suitable analog thereof to melanin, inthe presence of a lipid and an ultra-violet light absorbing compound,and isolating the resulting composition.

The novel composition of the present invention comprises melanin bondedto a lipid to form a lipomelanin. The structure is not clearlyunderstood, largely due to the lack of information about the synthesisand structure of melanins. As used herein, "lipomelanins" refers to thenovel compounds of the present invention, comprising one or more lipids(as hereinafter more fully described) bonded to one or more melanins. Asused herein, "lipomelanin sunscreen" comprises a lipomelanin bonded toan ultra-violet-light absorbing compound.

The lipomelanin sunscreen complex has been found to absorb UVR andparticularly short-wave UVB to a greater extent than melanin alone.Moreover, the inclusion of an ultra-violet absorbing compound to thereaction mixture during the formation of the lipomelanin advantageouslyprovides a sunscreen compound in which the absorption of both UVA andUVB may be varied by selecting and varying the number and properties ofultra-violet absorbing compound or compounds retained within thelipomelanin sunscreen. Thus, a lipomelanin sunscreen having a high levelof absorption of both UVA and UVB may be provided by incorporating theappropriate UV-absorbing compounds into the lipomelanin polymer.

The characteristics of the lipomelanin or the lipomelanin sunscreen ofthe present invention make it suitable for application to the skin.Specifically, it has the consistency of a smooth cream and thus may beeasily mixed with other creams for application to the skin. Itsconsistency also enables it to be spread evenly on the skin (eitheralone or in combination with other creams and ingredients) for uniformsunscreen protection. It is soluble at physiological pH making itsuitable for application to human skin. Furthermore, it is lessallergenic than other sunscreen compounds, thereby making it desirablefor use by those having sensitive skin.

In addition to the sunscreen and pigmentation functions of thelipomelanin and lipomelanin sunscreen, the compounds of the presentinvention may be useful for treatment of certain skin disorders such ashemangioma or vitiligo. Abnormal skin pigmentation and sensitivity toultra-violet light are associated with these and other disorders, andthe compounds of the present invention may function to provideadditional pigmentation or standardization of existing pigmentation toskin while still maintaining protection from UVR.

Additionally, the sunscreen and pigmentation aspects of the presentinvention make it suitable for use as a hair dye composition. Thelipomelanin composition can be applied to the hair to provide increasedpigmentation.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention will be described by reference tothe following figures in which

FIG. 1 shows the absorption spectra of unoxidized DOPA, at thewavelengths of from 260 to 440 nm.

FIG. 2 shows the absorption spectra of melanin and lipomelanin;

FIG. 3 shows the absorption spectra of melanin, paba-melanin,parsol-melanin and paba-parsol-melanin in the absence of an incorporatedlipid;

FIG. 4 shows the absorption spectra of lipomelanin, paba-lipomelanin,parsol-lipomelanin and paba-parsol-lipomelanin.

FIG. 5 shows the absorption spectra of melanin, paba-melanin andparsol-melanin, where the paba and parsol are added after the oxidationstep;

FIG. 6 shows the absorption spectra of lipomelanin, paba-lipomelanin andparsol-lipomelanin, where the paba and parsol are added after theoxidation step;

FIG. 7 shows the absorption spectra of lipomelanin (prepared withtyrosinase and by two preparation methods without tyrosinase); and

FIG. 8 shows the absorption spectra of lipomelanin with acetylsalicylicacid and either paba or benzophenone.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with one aspect of the invention, a lipomelanin isdisclosed. The lipomelanin is a compound prepared by oxidization of DOPAor a suitable DOPA analog in the presence of an unsaturated lipid (ashereinafter more fully described). The lipomelanin is creamy and smooth,suitable for application to human skin.

In a further aspect of this invention, a lipomelanin sunscreen isprovided. The lipomelanin sunscreen comprises melanin linked to a lipidand one or more ultra-violet-light absorbing compounds. The lipomelaninsunscreen thus provides protection from the harmful aspects of UVR,while additionally adding pigmentation to the skin of the user.

The term "lipid" as used herein is meant to encompass compoundsclassified as lipids including fats, phosphoglycerides and fatty acids.Lipids are organic compounds chiefly comprising carbon, hydrogen andoxygen, but may also include other elements. Lipids are insoluble inwater, but are soluble in various organic solvents. Included within thelipid family are fats, which are esters of glycerol which hydrolyze toform glycerol and fatty acids. Fatty acids are organic acids comprisingcarbon and hydrogen and including a carboxyl group. Phosphoglyceridesare similar to fats in which one fatty acid component has been replacedby a phosphoric acid component, and may additionally contain nitrogen.

Non-limiting examples of lipids for use as the lipid compound in thelipomelanin sunscreen of the present invention include unsaturated fattyacids; triglycerides; diglycerides; monoglycerides; methyl, ethyl,octyl, and higher molecular weight esters of fatty acids; lecithins (forexample phosphatidyl choline); cephalins (for example, phosphatidylethanolamine); phosphatidyl dimethylethanolamine; phosphatidyl;phosphatidyl inositol, phosphatidyl serine and phosphatidic acid.Preferably, the lipids of the present invention should be unsaturated(to provide covalent bonding sites), of high molecular weight, with anapproximate lower limit of a C₁₀ chain length. Preferred fatty acidsinclude but are not limited to long-chain fatty acids such asarachidonic acid, oleic acid, linoleic acid and linolenic acid.Preferred phosphoglycerides for use as the lipid compound in thelipomelanin sunscreen include lecithins.

The lipomelanin sunscreen may incorporate more than oneultra-violet-light absorbing compound. In this way, the effectiveness ofthe lipomelanin sunscreen may be maximized by incorporating within thelipomelanin polymer compounds which absorb in different wavelengths ofthe ultra-violet spectrum, for example, in both the short-wave UVB andin the long-wave UVA regions of the UVR spectrum.

The ultra-violet-light absorbing compound may be any compound whichabsorbs ultra-violet radiation and is suitable for application onto theskin. The United States FDA has disseminated a list of sunscreen andsunblocking agents considered safe and effective for both UVA and UVB.Non-limiting examples of such suitable ultra-violet absorbing compoundsfor incorporation into the lipomelanin sunscreen include paba, butylpaba, cinoxate, diethanolamine p-methoxycinnamate, digalloyl trioleate,dioxybenzone, amyl dimethyl paba, homomenthyl salicylate, ethyl4-aminobenzoate, ethyl 4- bis(hydroxypropyl)! aminobenzoate,2-Ethyl-hexyl 2-cyano-3,3-dephenylacrylate, ethyl-hexylp-methoxycinnamate, 2-Ethyl-hexyl salicylate, glycerol aminobenzoate,homosalate, lawsone with dihydroxyacetone, menthyl anthranilate,Padimate A, Padimate O, 2-Phenylbenzimidazole 5-sulfonic acid, redpetrolatum, acetylsalicylic acid, triethanolamine salicylate, octyldimethyl paba, glycerol paba, 2-hydroxy-4-methoxy-5-sulfobenzophenone(trihydrate) (Sulisobenzone), butyl methoxy benzoylmethane (Parsol1789), 4-tert-butyl-4'-methoxy-dibenzoylmethane,2-hydroxy-4-methoxybenzophenone (oxybenzone), isoamyl dimethyl pabaester, 4-hydroxycinnamic acid, benzophenone, and polymers orcombinations thereof.

Non-limiting examples of compounds appropriate for incorporation into alipomelanin sunscreen and known to specifically absorb UVA includeoxybenzone, sulisobenzone, dioxybenzone, menthyl anthranilate and Parsol1789.

Non-limiting examples of compounds appropriate for incorporation into alipomelanin sunscreen and known to absorb UVB include paba, amyldimethyl paba, glyceryl paba, octyl dimethyl paba, anthranilates,2-ethoxyethyl p-methoxycinnamate, diethanolamine p-methoxycinnamate,digalloyl trioleate, ethyl 4-bis-(hydroxypropyl) aminobenzoate,2-Ethyl-hexyl salicylate, glycerol aminobenzoate, homomenthylsalicylate, lawsone with dihydroxyacetone, 2-Phenyl benzimidazole5-sulfonic acid and triethanolamine salicylate.

The method for making a melanin sunscreen of the present inventionincludes oxidizing 3,4-dihydroxyphenylalanine (DOPA) to form melanin.Analogs of DOPA may also be used in accordance with the presentinvention. Suitable analog compounds may include synthetic analogs ornaturally occurring analogs. Non-limiting examples of DOPA analogsinclude hydroquinone, cathechol, o-quinone, p-quinone, DOPA methylester, dihydroxyphenylacetic acid, dihydroxyphenyl glycol anddihydroxyphenyl serine.

DOPA or an analog thereof may be oxidized by aeration. Thus, forexample, air is bubbled through a solution of DOPA in an alkalinemedium. The solution may also be aerated by rotary movement or shaking.The pH of the alkaline medium may be in the range of from about 7 toabout 10. Preferably, the alkaline medium has a pH of about 8.Non-limiting examples of a suitable alkaline medium include sodiumphosphate, potassium phosphate, sodium borate, and tris-hydroxymethyl-HCl. Most preferably, the alkaline medium is sodium phosphatebuffer at pH 8.0.

The lipid compound, either alone or in conjunction with one or moreultra-violet absorbing compounds is added to the DOPA solution andaeration on a rotary shaker is continued for a time sufficient tooxidize DOPA to form lipomelanin, at least overnight.

In another aspect of the present invention, the melanin may beenzymatically oxidized by tyrosinase. Tyrosinase oxidation occurs at anapproximate pH of 6.8, at temperatures of between 20° C. and 37° C.

Upon completion of the oxidation, the resulting lipomelanin isprecipitated by addition of inorganic acid to the solution. The acid isnot particularly restricted and may include any acid capable of reducingthe pH of the final suspension to a pH sufficient for precipitation ofthe complex, typically below 4, such as hydrochloric acid or sulphuricacid.

The precipitated lipomelanin is removed from the solution by any methodsuitable for separating solids from liquids. Centrifugation as well asfiltration are methods suitable to separate the lipomelanin from theacid medium. In order to purify the lipomelanin, the sediment may beredissolved in a suitable alkaline medium, as set out in the foregoing,and precipitated therefrom by the addition of acid. These purificationsteps are preferably repeated at least twice in order to removeimpurities from the lipomelanin.

The absorption spectra of the novel compounds prepared according to themethod of the present invention are noted in the Figures. By way ofreference, FIG. 1 shows the absorption spectra, at wavelengths of from260 to 440 nm, of unoxidized DOPA, together with a blank.

FIG. 2 presents the absorption spectra of melanin (oxidized from DOPA,without any lipid compounds) and the lipomelanin of the presentinvention, without any incorporated ultra-violet light absorbingcompound. As can be noted from FIG. 2, melanin has an increased abilityto absorb UVR over a broader range of wavelengths than does theunoxidized DOPA of FIG. 1. The lipomelanin of the present inventionprovides a UVR absorbance profile and quantity similar to that ofmelanin.

FIG. 3 shows the absorption spectra of various melanins withultra-violet light absorbing compounds. No lipid is included. The figureshows the spectra of: (a) melanin, (b) paba-melanin, (c) parsol-melaninand (d) paba-parsol melanin.

FIG. 4 is the absorption spectra of the lipomelanins of the presentinvention as follows: (a) lipomelanin without any ultra-violet lightabsorbing compounds, (b) paba-lipomelanin, (c) parsol-lipomelanin and(d) paba-parsol lipomelanin.

FIGS. 5 and 6 show the absorption spectra of various melanins andlipomelanins wherein the additional compounds (lipids and ultra-violetlight absorbing compounds) are added to the melanin mixture after theoxidation. As can be seen from FIGS. 5 and 6, the addition of compoundsafter oxidation results in melanin and lipomelanin-ultraviolet lightabsorbing compound mixtures having lesser and flatter absorption spectrathan the melanin and lipomelanin mixtures of FIGS. 3 and 4 where theadditional compounds are incorporated into the lipomelanin at the timeof oxidation.

FIG. 7 provides a comparison of lipomelanins prepared by the enzymaticoxidation of DOPA or oxidation of DOPA by aeration.

FIG. 8 shows the absorption spectra of melanins of the present inventionprepared by various procedures. These include (a) lipomelanin with ASAprepared via enzymatic conversion of DOPA, (b) lipomelanin with ASAprepared via aeration without tyrosinase, (c) lipomelanin with ASA andpaba prepared by aeration without tyrosinase, and (d) lipomelanin withASA and benzophenone prepared via aeration with tyrosinase.

As can be seen from FIG. 8, the incorporation of ASA into thelipomelanin polymer was increased using the aeration process of thepresent invention. Both paba and ASA were incorporated into thelipomelanin, although benzophenone is not incorporated in large amounts,and may also act to reduce ASA incorporation, due to its relativeinsolubility in water.

The textural characteristics of the lipomelanin sunscreen of the presentinvention make it suitable for application directly onto the skin. Thelipid component of the lipomelanin promotes absorption of thecomposition by the skin. In addition, the lipomelanin of the presentinvention is creamy and smooth at physiological pH, and suitable fortopical application.

A lipomelanin of the present invention may be combined with otheringredients to form a sunscreen composition. These ingredients mayinclude substances typically found within creams, oils, ointments andlotions applied to the skin. Further, the added ingredients may functionsimply as diluents, or may optionally function to integrate additionalutility into the composition. Coloring agents that may impart someadditional ultra-violet-light protective value may also be added such aszinc oxide or titanium dioxide. Non-limiting examples of suitableingredients for incorporation into such a composition include oils, suchas mineral oil, jojoba oil and mink oil, emollients, vitamins,fragrances, dyes, colouring agents, pigments, water and any otheringredients typically added to skin-care compositions.

Aspects of the present invention will now be described by reference tothe following specific non-limiting examples.

EXAMPLE 1 Enzymatic Preparation of Lipomelanin from DOPA

A solution containing 200 mg DOPA, 0.2 ml linoleic acid (0.642 mmoles,Sigma Chemical Company) and 20 mg purified mushroom tyrosinase(3,310-3,870 units/mg, Sigma Chemical Company) in 50 ml 0.05M phosphatebuffer (pH 6.8) was incubated with shaking and exposure to air at 37° C.for 16 hours. The lipomelanin was acidified to pH 3 and 1.0M andsedimented by centrifugation at 1,000 g for 10 min. The supernatant wasdiscarded and the melanin was dissolved in 10 ml 0.1M sodium hydroxidesolution. The lipomelanin was precipitated by adding 1.0M hydrochloricacid to pH 3.0. The lipomelanin was then sedimented by centrifugation at1,000 g for 10 minutes.

The lipomelanin was redissolved and resedimented by centrifugationfollowing the same procedure three times more. The lipomelanin was thensuspended in 5 ml water, and stored at 4° C. until further use.

EXAMPLE 2 Preparation of Lipomelanin by Autooxidation of DOPA

A solution containing 500 mg DOPA and 0.5 ml linoleic acid (SigmaChemical Company) in 250 ml 0.1M phosphate buffer at pH 8.0 wasprepared. Air was bubbled through the solution at room temperature(approximately 21° C.) for 16 hours. The lipomelanin was isolated bysedimenting, redissolving and resedimenting as described in Example 1.

Increased yields of lipomelanin can be achieved by autooxidation of DOPAusing the following procedure. A solution containing 200 mg DOPA in 50ml 0.1M phosphate buffer at pH 8.0 was aerated by bubbling air throughthe solution at room temperature for 3 hours. 0.2 ml linoleic acid wasthen added and aeration continued for a further sixteen hours. Thelipomelanin was isolated by sedimenting, redissolving and resedimentingas described in Example 1.

EXAMPLE 3 Preparation of Lipomelanin with Additional Compounds

A solution containing 0.5 g DOPA in 250 ml 0.1M phosphate buffer at pH8.0 was prepared. Air was bubbled through the solution at roomtemperature (approximately 21° C.) for 3 hours. 0.5 ml linoleic acid and0.5 g paba were added. Aeration continued for an additional 12 hours.The lipomelanin/paba sunscreen was isolated by sedimentation,redissolving, and resedimenting as described in Example 1.

The lipomelanin/paba sunscreen prepared according to Example 3 is creamyand smooth for use in accordance with the sunscreen compositions of thepresent invention. It is more soluble in water at neutral pH thanmelanins alone, and soluble for use in accordance with the sunscreens ofthe present invention. Absorption properties of the lipomelanin/paba inthe range of short wavelength UVB is high, as indicated in FIG. 4.

EXAMPLE 4 Preparation of Lipomelanin with Lecithin

A solution containing 200 mg DOPA, 0.642 mmoles lecithin and 20 mgpurified mushroom tyrosinase (3,310-3,870 units/mg, Sigma ChemicalCompany) in 50 ml 0.05M phosphate buffer (pH 6.8) was incubated withshaking and exposure to air at 37° C. for 16 hours. The lipomelanin wasacidified to pH 3.0 and 1.0M and sedimented by centrifugation at 1,000 gfor 10 min. The supernatant was discarded and the lipomelanin wasdissolved in 10 ml 0.1M sodium hydroxide solution. The lipomelanin wasprecipitated by adding 1.0M hydrochloric acid to pH 3.0. The lipomelaninwas then sedimented by centrifugation at 1,000 g for 10 minutes.

The lipomelanin was redissolved and resedimented by centrifugationfollowing the same procedure three times more. The lipomelanin was thensuspended in 5 ml water, and stored at 4° C. until further use.

EXAMPLE 5 Preparation of Lipomelanins with Two Ultraviolet-lightAbsorbing Compounds

A solution containing 200 mg (1.01 mmole) DOPA, in 50 ml PO₄ buffer atpH 8.0 was aerated by shaking for three hours at room temperature. 500mg of paba (3.65 mmoles) in 45 ml of PO₄ buffer and 0.2 ml (0.642mmoles) linoleic acid and 0.4 ml (2.38 mmoles) cinnamic acid ethyl esterwere then added. Aeration continued for a further 16 hours. Thelipomelanin/paba sunscreen was isolated as described in Example 1.

An alternate lipomelanin sunscreen incorporating paba and parsol wasprepared as follows. A solution containing 200 mg (1.01 mmole) DOPA, in50 ml PO₄ buffer at pH 8.0 was aerated by shaking for three hours atroom temperature. 500 mg of paba (3.65 mmoles) in 45 ml of PO₄ bufferand 0.2 ml (0.642 mmoles) linoleic acid and 0.2 ml Parsol 1789 were thenadded. Aeration continued for a further 16 hours. The lipomelaninsunscreen was isolated as described in Example 1. The absorptionspectrum of the resulting compound (paba-parsol-lipomelanin) is shown inFIG. 4.

Other embodiments or variations are possible within the sphere and scopeof the present invention. All such modifications and variations arebelieved to be within the sphere and scope of the present invention asdefined by the claims appended hereto.

We claim:
 1. A lipomelanin sunscreen comprising a melanin compoundsubstantially chemically bound to a substantially unsaturated lipid toform a lipomelanin in combination with an ultraviolet radiationabsorbing compound, and wherein said unsaturated lipid is selected fromthe group consisting of unsaturated fats, fatty acids,phosphoglycerides, or a combination of one or more of the same.
 2. Thesunscreen of claim 1, wherein the unsaturated lipid is selected from thegroup consisting of triglycerides, diglycerides, monoglycerides, estersof fatty acids, lecithins, cephalins, phosphatidyl ethanolamine,phosphatidyl dimethylethanolamine, phosphatidyl monomethylethanolamine,phosphastidyl inositol, phosphatidyl serine, phosphatidic acid,arachidonic acid, oleic acid, linoleic acid, linolenic acid, or acombination of one or more of the same.
 3. The sunscreen of claim 1,wherein the unsaturated lipid comprises linoleic acid.
 4. The sunscreenof claim 1 wherein said ultraviolet radiation absorbing compound issubstantially physically entrapped within the lipomelanin molecules. 5.The sunscreen of claim 1 wherein the ultraviolet radiation absorbingcompound is selected from the group consisting of paba, butyl paba,cinoxate, diethanolamine p-methoxycinnamate, digalloyl trioleate,dioxybenzone, amyl dimethyl paba, homomenthyl salicylate, ethyl4-aminobenzoate, ethyl 4-(bis(hydroxypropyl)) aminobenzoate,2-ethyl-hexyl 2-cyano-3, 3-dephenylacrylate, ethyl-hexylp-methoxycinnamate, 2-ethyl-hexyl salicylate, glycerol aminobenzoate,homosalate, lawsone with dihydroxyacetone, menthyl anthranilate,PADIMATE A, PADIMATE O, 2-phenylbenzimidazole 5-sulfonic acid, redpetrolatum, acetylsalicylic acid, triethanolamine salicylate, octyldimethyl paba, glycerol paba, 2-hydroxy-4-methoxy-5-sulfobenzophenone(trihydrate) (sulisobenzone), butyl methoxy benzoylmethane (PARSOL1789), 4-tert-butyl-4'-methoxy-dibenzoylmethane,2-hydroxy-4-methoxybenzophenone (oxybensone), isoamyl dimethyl pabaester, 4-hydroxycinnamic acid, benzophenone, polymers thereof andcombinations thereof.
 6. The sunscreen of claim 1 wherein theunsaturated lipid is linoleic acid and the ultraviolet radiationabsorbing compound is paba.
 7. The sunscreen of claim 1 in combinationwith an adjuvant accaptable for application to human skin.
 8. Thesunscreen of claim 7 wherein said adjuvant comprises one or morecompounds selected from the group consisting of mineral oil, jojoba oil,mink oil, emollients, vitamins, fragrances, dyes, coloring agents,pigments, and water.
 9. A method for creating a lipomelanin sunscreencomprising the steps:dissolving in water a compound selected from thegroup of melanin precursors consisting of DOPA and DOPA analogs, wherebyan aqueous solution is formed having a concentration of about 10 toabout 20 millimoles per liter; adding to the solution of melaninprecursors a solution containing a substantially unsaturated lipid andone or more ultraviolet radiation absorbing compounds to form a reactionmixture containing a concentration of about 6 to about 12 millimolesunsaturated lipid per liter, said unsaturated lipid selected from thegroup consisting of substantially unsaturated fats, phosphoglycerides,fatty acids or a combination of the same; reacting the reaction mixturein the presence of oxygen for a sufficient period of time to form asolution containing lipomelanin sunscreen; and isolating the lipomelaninsunscreen from the solution.
 10. The method of claim 9 wherein saidultraviolet radiation absorbing compound is selected from the groupconsisting of: paba, butyl paba, cinoxate, diethanolaminep-methoxycinnamate, digalloyl trioleate, dioxybenzone, amyl dimethylpaba, homomenthyl salicylate, ethyl 4-aminobenzoate, ethyl4-(bis(hydroxypropyl)) aminobenzoate, 2-ethyl-hexyl 2-cyano-3,3-dephenylacrylate, ethyl-hexyl p-methoxycinnamate, 2-ethyl-hexylsalicylate, glycerol aminobenzoate, homosalate, lawsone withdihydroxyacetone, menthyl anthranilate, PADIMATE A, PADIMATE O,2-phenylbenzimidazole 5-sulfonic acid, red petrolatum, acetylsalicylicacid, triethanolamine salicylate, octyl dimethyl paba, glycerol paba,2-hydroxy-4-methoxy-5-sulfobenzophenone (trihydrate) (sulisobenzone),butyl methoxy benzoylmethane (PARSOL 1789),4-tert-butyl-4'-methoxy-dibenzoylmethane,2-hydroxy-4-methoxybenzophenone (oxybensone), isoamyl dimethyl pabaester, 4-hydroxycinnamic acid, benzophenone, polymers thereof andcombinations thereof.
 11. The method of claim 9 wherein the DOPA analogsare selected from the group consisting of hydroquinone, cathechol,o-quinone, p-quinone, DOPA methyl ester, dihydroxyphenylacetic acid,dihydroxyphenyl glycol and dihydroxyphenyl serine.
 12. The method ofclaim 9, wherein the unsaturated lipid is linoleic acid.
 13. The methodof claim 9, wherein reacting the reaction mixture comprises thesteps:adding an enzyme to the reaction mixture; and agitating thereaction mixture in the presence of oxygen.
 14. The method of claim 13wherein the enzyme comprises tyrosinase.
 15. The method of claim 14wherein the concentration of said tyrosinase in the reaction Mixture isabout 20 to about 21 millimoles/liter, and the activity of saidtyrosinase is about 3,310 to about 3,870 units per milligram.
 16. Themethod of claim 15 wherein the pH of the reaction mixture is maintainedat about 6.7 by using a phosphate buffer in a concentration of about0.05 moles per liter, and the temperature of the reaction mixture ismaintained at about 37 degrees centigrade for a period of about 16hours.
 17. The method of claim 9 wherein reacting the reaction mixturecomprises the steps:controlling the pH in the range of about 6 to about10; and agitating the reaction mixture in the presence of oxygen. 18.The method of claim 17 wherein the pH is controlled within a range ofabout 8 to about
 10. 19. The method of claim 17 wherein the pH iscontrolled using a phosphate buffer at a pH of about
 8. 20. The methodof claim 17 wherein the step of agitating the reaction mixture in thepresence of oxygen is performed by bubbling air through the reactionmixture.
 21. The method of claim 17 wherein the reaction continues forat least about 12 to about 16 hours.
 22. A method for producing alipomelanin sunscreen by the autooxidization of a melanin precursor inthe presence of an unsaturated lipid and an ultraviolet radiationabsorbing compound, comprising the steps:dissolving in water a compoundselected from the group of melanin precursors, whereby an aqueoussolution having a concentration of about 10 to about 20 millimolesmelanin precursor per liter is formed; adding a solution containing anunsaturated lipid which is a fat, phosphoglyceride or fatty acid, or acombination thereof, and one or more ultraviolet radiation absorbingcompounds, to the aqueous solution to form a concentration of about 6 toabout 7 millimoles lipid per liter to form a reaction mixture; adding tothe reaction mixture an ultraviolet radiation absorbing compound;reacting the reaction mixture in the presence of oxygen for at leastabout 12 to about 16 hours to form a lipomelanin sunscreen in which theunsaturated lipid is substantially chemically bound to melanin, and inwhich the ultraviolet radiation absorbing compound is physicallyentrapped within the molecules of the lipomelanin.